Heart failure following a myocardial infarction (MI) continues to remain a leading killer in the western world. In the United States, the estimated annual incidence of myocardial infarction (MI) is 745,000 new and 410,000 recurrent episodes. There is a critical need to develop new therapies since end-stage heart failure is only treated through heart transplantation or left ventricular (LV) assist devices, and current pharmaceutical regimens do not adequately prevent post-MI negative LV remodeling. As an alternative to total heart transplantation, cellular cardiomyoplasty, or cell transplantation, has been explored for the treatment of MI and heart failure; however, more recently a cellular biomaterials have shown great promise in providing similar functional benefit without the complications associated with cell delivery. Biomaterial products have the key advantages of being off-the-shelf available and relatively inexpensive to manufacture. Existing materials have however been limited since none have been specifically designed for the myocardium, and none mimic the degraded post-MI extracellular matrix (ECM) they are intended to replace. The materials suffer from 1) their inability to be delivered via current catheter technology, and/or 2) their lack of complex, myocardial specific ECM cues, which promote repair. The material used for the Ventrix product is the first example of a myocardial-specific material that can be delivered via catheter to promote repair in the post-MI environment. This material is liquid at room temperature and forms a porous and fibrous scaffold upon injection into the myocardium. We have shown that it promotes cell influx, increases areas of surviving cardiomyocytes, and preserves LV geometry and cardiac function in a rat MI model, and can be delivered through a percutaneous transendocardial approach in a porcine model. In our Phase I SBIR, we demonstrated that VentriGelTM increased cardiac muscle, improved cardiac function, and prevented negative LV remodeling following catheter based delivery in a porcine MI model. The studies proposed in Phase II are part of the final steps to initiate studying VentriGelTM in patients, and a key step i bringing a biomaterial product to market, which will be complementary or mostly parallel to the current MI pharmaceutical market. In Phase II, we will achieve the following two specific aims to reach our goals: 1) To demonstrate an improvement in cardiac function and negative LV remodeling following delivery of VentriGel post-myocardial infarction and to determine its optimal volume and delivery time window in a porcine acute myocardial infarction model and 2) To assess safety of VentriGel via toxicology studies required for IND submission to the FDA. The objective of the proposed project is to complete the key preclinical studies for VentriGelTM to translate to the clinic. This will be the first catheter deliverable regenerative biomaterial product for treating the millions of patients suffering from MI.